Basics
Description
Plague is an enzootic disease transmitted by fleas from wild rodents and caused by Yersinia pestis. Humans and their pets can enter this cycle, resulting in human plague. Human plague has 3 main forms: bubonic, septicemic, and pneumonic; rarely presents as meningeal, pharyngeal, ocular, or gastrointestinal (GI) plague
Epidemiology
- Worldwide: enzootic in Africa, Asia, and Americas. Since 2000, 95% of the 22,000 cases reported to the World Health Organization have been from countries in sub-Saharan Africa.
- In the United States, most cases occur in Arizona, New Mexico, California, Colorado, Oregon, and Nevada.
- In the United States, most cases occur in spring/summer.
- 51 cases of plague occurred in the United States from 2004 to 2011.
- 20% of U.S. cases with identified mode of transmission are acquired through direct contact with Y. pestis " infected animals, not via flea bite.
- No cases of person-to-person transmission of pneumonic plague have been reported in the United States since 1924.
- Untreated bubonic plague: >50% fatal
- Untreated pneumonic plague: nearly 100% fatal
General Prevention
- Reduce rodent shelter and food sources in the immediate vicinity of the home by storing grain and animal food in rodent-proof containers.
- Flea disinfestation of cats and dogs, especially in endemic areas
- Hospital isolation precautions
- Patients with bubonic or septicemic plague and no evidence of pneumonia: standard precautions; add droplet precautions for first 24 hours of therapy until chest radiograph persistently clear.
- Patients with pneumonic plague: standard and droplet precautions. Continue droplet precautions until patient has completed 48 hours of appropriate antimicrobial therapy.
- Postexposure management
- All persons with exposure to known or suspected plague source in last 6 days
- Daily surveillance for fever or symptoms of disease for 7 " 10 days
- Offer prophylaxis.
- Initiate treatment if becomes ill
- Persons with close (<2 m) contact with a patient with pneumonic plague should receive antimicrobial prophylaxis, but isolation is not necessary.
- Chemoprophylaxis ≥8 years
- Doxycycline (PO), OR
- Ciprofloxacin (PO) at treatment doses for 7 days from last exposure (see "Medications " for dosing)
- Chemoprophylaxis <8 years: ciprofloxacin (PO)
- Notify state public health authorities of cases of suspected and proven Y. pestis infection.
- Vaccination is no longer available and is not considered useful to prevent plague from an enzootic source.
Pathophysiology
- Skin portal of entry
- Y. pestis is transmitted from fleas to humans via the regurgitation of the organism into the bite during the flea 's blood meal (Y. pestis blocks foregut, causing regurgitation).
- Rodents, ground squirrels, cats, prairie dogs, marmots, rabbits, and occasionally dogs harbor infected fleas and are reservoirs of infection (enzootic).
- Direct skin inoculation of organisms from infected animal tissue or blood occurs through breaks in the skin (e.g., cat scratch, skinning quarry).
- Lymphatic spread of infection to the regional lymph nodes creates a localized inflammatory response (bubo, bubonic).
- Subsequent hematogenous spread of the organism to other organs results in high levels of circulating bacterial endotoxin (septicemic plague).
- By hematogenous spread to lungs, both bubonic and septicemic plague can cause secondary pneumonic plague.
- Respiratory portal of entry
- Primary pneumonic plague: acquired via inhalation of respiratory tract droplets from a human or animal (e.g., cat) with pneumonic plague
- Incubation period
- 2 " 8 days for bubonic or septicemic plague
- 1 " 6 days for pneumonic plague
Etiology
Plague is caused by Y. pestis, a pleomorphic, bipolar-staining, gram-negative coccobacillus.
Diagnosis
History
- A thorough travel history (especially to enzootic areas) is imperative to raise the index of suspicion for diagnosing plague.
- Environmental history should include epizootic deaths (die-offs) of rodents, ground squirrels, or prairie dogs in the patient 's locale.
- In enzootic areas, a sick household cat or dog is an additional risk factor.
- Signs and symptoms
- Bubonic plague
- Initial symptom: pain in the groin or axillae prior to lymph node swelling
- Lymphadenitis (usually inguinal > axillary > cervical)
- Fever, chills, prostration
- Septicemic plague
- Tachycardia and hypotension
- Abdominal symptoms
- Hemorrhage
- Fever, chills, prostration
- Bubonic or septicemic plague may progress to secondary pneumonic plague.
- Pneumonic plague
- Cough, dyspnea
- Systemic manifestations
- Fever, chills, shock
- Rapidly progressive and often fatal
Physical Exam
- Tachycardic, hypotensive, tachypneic, and toxic-appearing
- Flea bite lymphadenitis classically affects inguinal nodes; cat-associated plague affects mostly axillary or cervical nodes secondary to handling infected cat.
- GI: Abdominal pain, nausea, and diarrhea are common, secondary to inflammatory mediators.
- Neurologic: weakness, delirium, and coma, owing to the effects of the endotoxin of Y. pestis
- Heme: disseminated intravascular coagulation
- Renal: glomerular parenchymal damage
- Rare: meningitis, endophthalmitis, endocarditis, and pleuritis
Diagnostic Tests & Interpretation
Lab
- Total WBC count
- Usually 10,000 " 20,000, but may be as high as 100,000, with immature neutrophils.
- Perform Gram, Wayson, Giemsa, or fluorescent antibody staining on specimen (blood, bubo, CSF, sputum) to look for gram-negative, bipolar-staining organisms.
- Y. pestis culture (Notify receiving lab.)
- Suspect bubonic plague: needle aspiration of the bubo for stain and culture. Puncture center of bubo with a sterile syringe and inject 1 mL of nonbacteriostatic, sterile saline. Withdraw aspirate vigorously until blood-tinged liquid appears in syringe.
- Suspect pneumonic plague: sputum for stain and culture
- Blood cultures are usually positive, even with bubonic plague, and should always be done prior to therapy.
- Slow-grower; may be misidentified as Yersinia pseudotuberculosis or Acinetobacter sp.
- Serology
- Single positive acute serology OR
- At least a 4-fold increase in antibody titers by passive hemagglutination test between acute and convalescent sera taken 4 " 12 weeks apart
- Comprehensive testing and notification to state public health lab and CDC
Diagnostic Procedures/Other
Pitfalls
- Patients who present with a nonspecific febrile illness, tachycardia, and tachypnea, rather than lymphadenitis, are at higher risk for delayed diagnosis and serious sequelae (e.g., septicemic plague, death).
- Failure to consider septicemic plague in the appropriate epidemiologic setting and withholding appropriate antibiotics or using an empiric ²-lactam regimen
- Failure to treat suspected bubonic plague with antibiotics while awaiting culture results when needle aspiration of the bubo shows no organisms on direct stain.
Differential Diagnosis
- Diagnosis of plague follows a high index of suspicion and a thorough review of the patient 's lifestyle, travel history, and recent activities. The appearance of septicemia and endotoxin-mediated shock includes a large differential diagnosis that includes sepsis owing to other bacteria or viruses as well as distributive shock resulting from toxic ingestion or anaphylaxis.
- Infection
- Streptococcal and staphylococcal infections (especially between the toes) can result in tender inguinal lymph nodes, fever, shock.
- Cat-scratch fever (Bartonella henselae) can present with a history of cat scratch or bite, regional lymphadenitis, and fever.
- Hantavirus in humans has a clinical presentation similar to septicemic and pneumonic plague and occurs in many of the plague-enzootic areas.
- Rickettsial diseases: Rickettsia, Orientia, Coxiella, Ehrlichia, Anaplasma (e.g., Rocky Mountain spotted fever [Rickettsiarickettsii] and relapsing tick fever due to Borrelia sp. may mimic septicemic or pneumonic plague)
- Recent reports of plague-like illnesses have been associated with infections by other organisms such as Burkholderia pseudomallei (melioidosis) and Francisella tularensis (tularemia).
Treatment
Medication
- Use IV/IM forms for acute disease.
- For children, gentamicin or streptomycin administered intramuscularly or intravenously appear to be equally effective.
- Gentamicin, equally effective as streptomycin in recent study (IV): peds: 2.5 mg/kg/dose q8h. Adult: 5 mg/kg/dose q24h
- Streptomycin traditionally has been the drug of choice (IV/IM): peds: 20 " 30 mg/kg/24 h divided q12h. Adult: 15 mg/kg/dose q12h to max 1 g q12h
- Meningitis or severe disease: Consider adding chloramphenicol (IV): 12.5 " 25 mg/kg/dose q6h (max 4 g/24 h). Monitor for toxicity.
- Alternatives
- Doxycycline: peds (IV/PO): 2.2 mg/kg q12h up to adult dose as the max dose. Adult: 200 mg IV 1, then 100 mg IV/PO q12h. Some experts recommend adding it to gentamicin for severe disease.
- Ciprofloxacin: peds (IV/PO): 30 mg/kg/24 h (max 1 g/24 h) divided q12h. Adults: 400 mg IV q12h; 500 mg PO q12h
- Continue antibiotic therapy for 7 " 10 days or until several days after lysis of fever.
- Severely ill patients may require a substantially longer course of therapy.
- Foci (e.g., abscess) are infectious until sufficient appropriate antimicrobial therapy is given.
Additional Treatment
General Measures
For septic patients in shock, initial attention should be given to airway management and fluid resuscitation, then antibiotics.
Ongoing Care
Follow-up Recommendations
Resolution of symptoms should begin in the first 3 days after initiation of therapy; however, the rate of clinical improvement depends on the initial severity of illness.
Patient Monitoring
None; most recover without sequelae.
Complications
- Hematologic (disseminated intravascular coagulation)
- Renal (glomerular and parenchymal damage)
Additional Reading
- Butler T. Plague into the 21st century. Clin Infect Dis. 2009;49(5):736 " 742. [View Abstract]
- Centers for Disease Control and Prevention. Plague. www.cdc.gov/plague/. Accessed February 2, 2015.
- Gage KL, Dennis DT, Orloski KA, et al. Cases of cat-associated human plague in the western US, 1977 " 1998. Clin Infect Dis. 2000;30(6):893 " 900. [View Abstract]
- Koirala J. Plague: disease, management, and recognition of act of terrorism. Infect Dis Clin North Am. 2006;20(2):273 " 287. [View Abstract]
- Raoult D, Mouffok N, Bitam I, et al. Plague: history and contemporary analysis. J Infect. 2013;66(1):18 " 26. [View Abstract]
Codes
ICD09
- 020.9 Plague, unspecified
- 020.0 Bubonic plague
- 020.2 Septicemic plague
- 020.5 Pneumonic plague, unspecified
- 020.1 Cellulocutaneous plague
- 020.4 Secondary pneumonic plague
- 020.8 Other specified types of plague
- 020.3 Primary pneumonic plague
ICD10
- A20.9 Plague, unspecified
- A20.0 Bubonic plague
- A20.7 Septicemic plague
- A20.2 Pneumonic plague
- A20.1 Cellulocutaneous plague
- A20.8 Other forms of plague
- A20.3 Plague meningitis
SNOMED
- 58750007 Plague (disorder)
- 50797007 Bubonic plague (disorder)
- 9012003 Septicemic plague (disorder)
- 38976008 Pneumonic plague (disorder)
- 35339003 Primary pneumonic plague
- 43484003 Cellulocutaneous plague
- 186284005 Plague meningitis (disorder)
- 240384004 Gastroenteric plague (disorder)
FAQ
- Q: Can one determine the risks of being exposed to plague during international travel?
- A: Yes. The CDC provides a service that contains updated information for international travel exposures at www.cdc.gov/travel.
- Q: Does persistent fever during treatment for plague warrant altering the antibiotic regimen?
- A: No. Fever can persist for up to 2 weeks despite appropriate 1st-line antibiotic therapy for Y. pestis. However, an evaluation for a focus of infection requiring drainage is recommended under these circumstances.
- Q: What is a bubo?
- A: "Bubo " (plural: buboes) comes from the Greek word for groin. A bubo is a painful, swollen lymph node.